title: MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells.
abstract: Mutation in huntingtin (HTT) gene causes Huntington's disease (HD). Expression of many micro RNAs is known to alter in cell, animal models and brains of HD patients, but their cellular effects are not known. Here, we show that expression of microRNA-124 (miR-124) is down regulated in HD striatal mutant STHdh(Q111)/Hdh(Q111) cells, a cell model of HD compared to STHdh(Q7)/Hdh(Q7) cells. STHdh(Q7)/Hdh(Q7) and STHdh(Q111)/Hdh(Q111) cells express endogenously full length wild type and mutant HTT respectively. We confirmed this result in R6/2 mouse, an animal model of HD, expressing mutant HTT. Gene Ontology terms related to cell cycle were enriched significantly with experimentally validated targets of miR-124. We observed that expression of Cyclin A2 (CCNA2), a putative target of miR-124 was increased in mutant STHdh(Q111)/Hdh(Q111) cells and brains of R6/2 mice. Fraction of cells in S phase was higher in asynchronously growing mutant STHdh(Q111)/Hdh(Q111) cells compared to wild type STHdh(Q7)/Hdh(Q7) cells and could be altered by exogenous expression or inhibition of miR-124. Exogenous expression or knock down of CCNA2, a target of miR-124, also alters proportion of cells in S phase of HD cell model. In summary, decreased miR-124 expression could increase CCNA2 in cell and animal model of HD and is involved in deregulation of cell cycle in STHdh(Q111)/Hdh(Q111) cells.
authors.affiliation: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics SINP, 1/AF Bidhan Nagar, Kolkata 700 064, India.
authors.forename: Eashita
authors.initials: E
authors.lastname: Das
authors.forename: Nihar Ranjan
authors.initials: NR
authors.lastname: Jana
authors.forename: Nitai Pada
authors.initials: NP
authors.lastname: Bhattacharyya
mesh_terms: D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D003342:Corpus Striatum / Q000378:metabolism; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C508184:CCNA2 protein, mouse; D056751:Cyclin A2; D017931:DNA Primers; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D034741:RNA, Small Interfering
keywords: 3′-UTR; 3′-untranslated region; CCNA2; Cell cycle; Cyclin A2; HD; Huntington’s disease; MicroRNA-124; STHdh(Q111)/Hdh(Q111) cells; STHdh(Q7)/Hdh(Q7) cells; miRNA; micro RNA